Targeted delivery to the hair follicle

[Dave001]

It is possible to select a carrier particle size to cause a forced route of entry through the hair follicle. The optimal particle size range has been consistently repeated in numerous studies, and the sizes have been further characterized by the depth to which they are able to penetrate. Penetration through the stratum corneum is prevented in this range. Stating the range without providing details concerning the hair follicle region targeted would be somewhat meaningless, but in general the optimal size appears to fall within the range of 1-7 µm.

Moreover, certain microspheres can better maintain their structural integrity than others. Phospholipid vesicles, for example, are quite "malleable", which may not be desirable for some applications. In summary, we're on the horizon of a new era in targeted drug delivery.

 

[Jacob]

Glad you could join us :shock:

 

[Radio]

I use a cloth.

 

[Britannia]

We are indeed on a new era in targeted drug therapy, check this site out for some interesting info: http://www.durect.com/wt/durect/page_name/delivery
Im not sure exactly how much this is going to benefit male pattern baldness sufferers though, it is certainly good news for cancer patients. Conventional cytotoxic drugs often have widespread effects throughout the body, in theory targeted drug delivery would reduce adverse effects and allow greater strength cytotoxic drugs to fight the neoplastic cells.
Like I said its interesting but not sure how it will benefit male pattern baldness sufferers, in the near future anyway. I doubt many drug companies are going to be running to develop a drug with targeted action for male pattern baldness.

 

[Dave001]

Glad you could join us :shock:

Huh? I don't have multiple orgasms from thinking about liposomes like you do.

Targeted follicular delivery has long been a topic of interest, but only very recently has the quantitive in vivo data grown sufficient to impress me, and it isn't particularly or even generally phospholipid carriers that I think have the most utility for our application.

 

[Jacob]

I'm glad you figured out what I was getting at 8) And I'm glad you're finally impressed. I haven't just talked about liposomes(check Hairsite) and it didn't take me this long. In fact certain folks(ahem) thought plain ole delivery systems were just fine..nothing else was needed.

This is the stuff lipoxidil is working with: http://www.salvona.com/sal_technol/ste_nanosal.php

 

[Dave001]

I'm glad you figured out what I was getting at 8)

Which would be what?

And I'm glad you're finally impressed. I haven't just talked about liposomes(check Hairsite) and it didn't take me this long. In fact certain folks(ahem) thought plain ole delivery systems were just fine..nothing else was needed.

Err, my general attitude toward targeting of the hair follicle/pilosebaceous unit is the same as it has always been. Only now is the amounting data beginning to have substantial predictive value. There's nothing inherently wrong with "plain ole delivery systems" either. New and expensive doesn't mean better. It might be in one instance; it might not be in the next. Reduced expensive and ease of manufacturing are also important developments. Far too often though, the vehicle is dismissed as a relatively unimportant concern in the delivery of dermatological agents -- not even an afterthought.

My post was prompted by some very recent studies concerning the in vivo determination of particle size and distribution in human hair follicles, at least one of which may not yet even be indexed by PubMed. It was published this month, so it's unlikely old news. If anyone wants the cites, ask me in a couple of days, after I've had the chance to sort through and import them into my bibliographic manager.

This is the stuff lipoxidil is working with: http://www.salvona.com/sal_technol/ste_nanosal.php

Nanometer sized particles readily penetrate through the stratum corneum. That's not follicular targeting. It's marketing. It's targeted marketing, directed at those who are impressed by the sound of units with prefixes appearing lower on the SI scale. What is the basis of their vehicle design? What is the body of research that supports their selection?

Lipoxidil has never been what I'd call on top of the science. The last time I checked they were sold on the infamous Oh and [not so] Smart mouse study, in which the authors confused the body/scalp hair relationship and concluded that topical anti-estrogens represented a potential treatment for androgenetic alopecia.

 

[Jacob]

Like I said...glad you could join us. I hope Bryan will be next.

As for your questions to Lipoxidil...why don't you ask them? Or better yet, ask Salvona. I'm sure many will be relieved to know Salvona is the one who made their latest product. In the past ppl whined about- oh, lipoxidil must make it themselves..probably in a kitchen or whatever.

I should have mentioned, for those interested, to scroll down a bit to read up on the Nanosal: http://www.salvona.com/sal_technol/ste_nanosal.php

 

[Dave001]

Like I said...glad you could join us. I hope Bryan will be next.

I'm still not sure what you mean by that. I've repeated several times now that my position on this issue has remained consistent.

I should have mentioned, for those interested, to scroll down a bit to read up on the Nanosal: http://www.salvona.com/sal_technol/ste_nanosal.php

Nano-. Maybe they are targeting the ovarian follicle with semen-loaded nanospheres. I sure wouldn't want to apply it to my scalp.

 

[Jacob]

Next time read the information provided instead of pretending to know it all and calling it "targeted marketing". Then you won't have to resort to asinine comments such as your last one there.

Again..welcome aboard.

 

[Old Baldy]

Jacob, Dave wrote: "Nanometer sized particles readily penetrate through the stratum corneum. That's not follicular targeting"

He's right. You want to allow the "medicine" to get into the follicle and STAY there long enough to make a difference. We're not there yet, but from what Dave and Tren have found, maybe we're getting closer. But we're not there yet.

I have to admit that from my layman's viewpoint, it seems to be impossible to ever fully achieve that goal. But.... it appears I'm probably wrong.

 

[Jacob]

Jacob, Dave wrote: "Nanometer sized particles readily penetrate through the stratum corneum. That's not follicular targeting"

He's right. You want to allow the "medicine" to get into the follicle and STAY there long enough to make a difference. We're not there yet, but from what Dave and Tren have found, maybe we're getting closer. But we're not there yet.

I have to admit that from my layman's viewpoint, it seems to be impossible to ever fully achieve that goal. But.... it appears I'm probably wrong.

He's right but he's wrong. If you read what Nanosal is capable of doing you'll see why. Nanosal CAN be "follicular targeting". They DO "stick" around there. Then they're time released..etc etc.

More info somewhere in this pdf: http://www.midwestscc.org/archives/march05.pdf
Starts on page 14

NanoSal is distinct from other microspheres, nanospheres, nano-capsules or lipospheres. The active is uniformly dispersed in a customized blend of a solid polymeric matrix system with a 50% payload. The matrix retains the active, preventing pre-mature release. The system is said to be more stable than liposomes. The surface of these sub-micron spheres can be made cationic or bioadhesive to adhere to human endothelium cells or to hair.

It is even supposed to work in shampoo.

 

[Old Baldy]

Interesting, thanks for the info.!

I read the link Jacob, can you direct me to the part that states medicines can be delivered into the follicle. Or is this to be inferred due to better absorption and "sticking around"?

Either way, this micro encapsulation method has become reality. I've noticed Retin A comes in a Retin A Micro formulation.

Jacob, can you get me a bottle of that stuff which is "pictured" in your link? (I want some NanoSal!!) :lol:

http://www.salvona.com/sal_technol/ste_nanosal.php

 

[Jacob]

If there's money involved...I'll get you some 8)

On another part of the site it says:

Ingredients such as vitamins and anti-aging agents need to reach the treatment site and penetrate into deeper layers of the hair and scalp to be effective. Unfortunately, most of these therapeutic ingredients existed in free form in the product usually wind up down the drain. NanoSalâ„¢ is proven to deposit product ingredients on hair after washing.

But we already know liposomes do this. "The term "follicle targeting system" describes a liposomal formulation that facilitates the transport of active ingredients (e.g. lactic acid) into the follicle." ( http://www.eucerin.co.uk/product_info/galenics.html )

According to the present methods, liposomes preferentially deliver the beneficial compounds to the hair follicles where the compounds enter into the follicle cells. By virtue of the selectivity of the liposome-mediated delivery method, the administered compounds are not delivered substantially to the dermis or internally to the circulation, thereby minimizing undesirable side effects that the administered compound might exert on such dermis tissue or systemically in the circulation.

( http://www.pharmcast.com/Patents/Yr2001 ... 050101.htm )

And all this reminds me of the laminaria extract and the "bulge region":

The mechanism of hair growth has been clarifying itself by the improvement in the culture techniques for hair follicle cells. Recently stem cells inducing the anagen phase in the hair follicle cycle have been discovered in the bulge region of the outer root sheath (ORS). To find growth-promoting agents for the ORS cells, we evaluated the effect of various botanical extracts on the growth of cultured human hair follicles. We found that Laminaria angustata extract increased the ORS cell growth. Further, hair-growth in the shaved skin of C3H mice was also promoted by the topical application of the extract.

Notice they didn't talk about using a liposomal type carrier.

I've emailed Salvona regarding this though. Hopefully they'll respond.

BTW..don't think for a minute that I think that this Nanosal is the best out there or will be the best. Some of the things I and others have posted about probably still aren't readily available. And I'd be willing to bet a couple of guys here wouldn't think they'd be too cost-effective :lol:

BTW Dave..I'd like to see whatever you were referring to. I'm sure others would as well.

 

[Dave001]

I have to admit that from my layman's viewpoint, it seems to be impossible to ever fully achieve that goal. But.... it appears I'm probably wrong.

I want to clarify that I was not alluding to any sort of revolutionary new technology. The actual *technology* to deliver the drugs in a targeted manner has been around for decades. The important progress that I was trying to highlight is the development and refinement of better techniques for measuring drug deposition in the hair follicle and pilosebaceous unit in humans. That can help us when faced with a choice between otherwise arbitrary topical vehicles.

We're still far from the point where we can incorporate a drug like flutamide into a vehicle and safely assume that it's not going to be absorbed systemically. Absorption is still going to be dependent on the active substance, and the vehicle itself depends on a number of factors beyond particle size.

Considering that most vehicles are chosen rather arbitrarily (most people aren't going to fund a human study for every substance they apply to their scalp), it makes sense to use the available data when selecting an otherwise arbitrary vehicle. That's the main implication of the new data for most of us: it can possibly help us to make a better guess. But a guess is still a guess.

 

[Dave001]

We are indeed on a new era in targeted drug therapy, check this site out for some interesting info: http://www.durect.com/wt/durect/page_name/delivery
Im not sure exactly how much this is going to benefit male pattern baldness sufferers though, it is certainly good news for cancer patients. Conventional cytotoxic drugs often have widespread effects throughout the body, in theory targeted drug delivery would reduce adverse effects and allow greater strength cytotoxic drugs to fight the neoplastic cells.
Like I said its interesting but not sure how it will benefit male pattern baldness sufferers, in the near future anyway. I doubt many drug companies are going to be running to develop a drug with targeted action for male pattern baldness.

A "miniaturized catheter"? This thread is about targeted hair follicle delivery. Just how mini are we talking?

 

[Britannia]

We are indeed on a new era in targeted drug therapy, check this site out for some interesting info: http://www.durect.com/wt/durect/page_name/delivery
Im not sure exactly how much this is going to benefit male pattern baldness sufferers though, it is certainly good news for cancer patients. Conventional cytotoxic drugs often have widespread effects throughout the body, in theory targeted drug delivery would reduce adverse effects and allow greater strength cytotoxic drugs to fight the neoplastic cells.
Like I said its interesting but not sure how it will benefit male pattern baldness sufferers, in the near future anyway. I doubt many drug companies are going to be running to develop a drug with targeted action for male pattern baldness.

A "miniaturized catheter"? This thread is about targeted hair follicle delivery. Just how mini are we talking?

Sorry that is the wrong link! The correct link is:
http://www.durect.com/wt/durect/page_name/transdur_tech

 

[Old Baldy]

I have to admit that from my layman's viewpoint, it seems to be impossible to ever fully achieve that goal. But.... it appears I'm probably wrong.

I want to clarify that I was not alluding to any sort of revolutionary new technology. The actual *technology* to deliver the drugs in a targeted manner has been around for decades. The important progress that I was trying to highlight is the development and refinement of better techniques for measuring drug deposition in the hair follicle and pilosebaceous unit in humans. That can help us when faced with a choice between otherwise arbitrary topical vehicles.

We're still far from the point where we can incorporate a drug like flutamide into a vehicle and safely assume that it's not going to be absorbed systemically. Absorption is still going to be dependent on the active substance, and the vehicle itself depends on a number of factors beyond particle size.

Considering that most vehicles are chosen rather arbitrarily (most people aren't going to fund a human study for every substance they apply to their scalp), it makes sense to use the available data when selecting an otherwise arbitrary vehicle. That's the main implication of the new data for most of us: it can possibly help us to make a better guess. But a guess is still a guess.

I understand Dave. But, maybe if you vary vehicles you get the same "non-tolerance" benefits that you get when you vary "medicines"?

You know, keep the scalp "guessing". Never let it set up it's negative "defenses" against my treatments so to speak. My disease apparently sets up this negative genetic "attack" on things that want to reverse male pattern baldness? That, I would think includes delivery vehicles as much as "medicines"?

Gentically, my scalp "wants" to go bald. I believe tolerance, at all levels, should be avoided. Just a guess. I don't really know.

 

[Dave001]

Jacob wrote:

> On another part of the site it says:
>
>

Ingredients such as vitamins and anti-aging agents need to
> reach the treatment site and penetrate into deeper layers of the hair
> and scalp to be effective. Unfortunately, most of these therapeutic
> ingredients existed in free form in the product usually wind up down
> the drain. NanoSalâ„¢ is proven to deposit product ingredients on hair
> after washing.

What is the significance of this claim?

> But we already know liposomes do this. "The term "follicle targeting
> system" describes a liposomal formulation that facilitates the
> transport of active ingredients (e.g. lactic acid) into the
> follicle." ( http://www.eucerin.co.uk/product_info/galenics.html )

More precisely, that's the term chosen by the maker of Eucerin,
presumably to describe one of their products.

>

According to the present methods, liposomes preferentially
> deliver the beneficial compounds to the hair follicles where the
> compounds enter into the follicle cells. By virtue of the selectivity
> of the liposome-mediated delivery method, the administered compounds
> are not delivered substantially to the dermis or internally to the
> circulation, thereby minimizing undesirable side effects that the
> administered compound might exert on such dermis tissue or
> systemically in the circulation.

(
> http://www.pharmcast.com/Patents/Yr2001 ... 050101.htm
> )

There is certainly reason to think they can under some conditions, yes.

> And all this reminds me of the laminaria extract and the "bulge
> region":

The mechanism of hair growth has been clarifying
> itself by the improvement in the culture techniques for hair follicle
> cells. Recently stem cells inducing the anagen phase in the hair
> follicle cycle have been discovered in the bulge region of the
> outer root sheath (ORS). To find growth-promoting agents for the
> ORS cells, we evaluated the effect of various botanical extracts on
> the growth of cultured human hair follicles. We found that Laminaria
> angustata extract increased the ORS cell growth. Further, hair-growth
> in the shaved skin of C3H mice was also promoted by the topical
> application of the extract.

I don't see any connection between the latter two quotes above.

> Notice they didn't talk about using a liposomal type carrier.

So what's your point?

> BTW..don't think for a minute that I think that this Nanosal is the
> best out there or will be the best. Some of the things I and others

I don't have any reason to think it does anything at all.

 

[Dave001]

I understand Dave. But, maybe if you vary vehicles you get the same "non-tolerance" benefits that you get when you vary "medicines"?

You know, keep the scalp "guessing". Never let it set up it's negative "defenses" against my treatments so to speak. My disease apparently sets up this negative genetic "attack" on things that want to reverse male pattern baldness? That, I would think includes delivery vehicles as much as "medicines"?

Gentically, my scalp "wants" to go bald. I believe tolerance, at all levels, should be avoided. Just a guess. I don't really know.

I don't think your scalp is giving the matter nearly as much thought as you suggest. As far as the barrier is concerned, the most sensible approach is to avoid too much irritation, and take ocassional breaks, etc.